Experimental Retinal Vein Occlusion Research Articles

Differences in collateral vessel formation after experimental retinal vein occlusion in spontaneously hypertensive rats and wild-type rats

ObjectiveRetinal vein occlusion (RVO) can lead to visual impairment, but the development of collateral vessels can sometimes mitigate significant damage. This study aimed to investigate the relationship between collateral vessels and hypertension, the most common underlying condition associated with RVO, by comparing spontaneously hypertensive rats (SHRs) and wild-type Wister rats (WWRs). We also examined the differences between WWRs and SHRs in terms of sphingosine 1-phosphate receptor 1 (S1PR1) expression and its product nitric oxide synthase 3 (NOS3) expression, which are involved in the formation of collateral vessels after vascular occlusion. MethodsLaser photocoagulation (PC) was used to occlude one randomly selected retinal vein in WWRs and SHRs, and the area surrounding the occluded vessel was examined using optical coherence tomography angiography. If reperfusion of the occluded vessel occurred within 2 weeks, the vessel was re-occluded repeatedly by PC. The number of eyes with successfully occluded vessels accompanied by collateral vessels was recorded. Then, WWRs and SHRs were divided into the following four groups: 1) control (no treatment), 2) vehicle (20% DMSO), 3) S1PR1 agonist (2 mg/mL SEW2871), and 4) S1PR1 antagonist (0.25 mg/mL VPC 23019) groups. The drugs were administered intravitreally in all groups except the control. The number of laser shots required for successful RVO was recorded. Histological evaluation and quantitative real-time PCR of S1PR1 and NOS3 were performed to elucidate the mechanisms underlying collateral vessel formation. ResultsThe proportion of eyes achieving successful vein occlusion was lower in SHRs (4/12 eyes, 33.3%) than in WWRs (8/10 eyes, 80%, p = 0.043). NOS3 expression at 6 h after PC was significantly higher in WWRs than in SHRs (p = 0.021). In WWRs treated with SEW2871, vein occlusion failed in 7 of 10 eyes (70%). The expression of NOS3 was significantly higher in the SEW2871 treatment group than in the untreated group (p < 0.001). Furthermore, NOS3 expression was significantly higher after SEW2871 treatment in WWRs than in SHRs (p = 0.011). ConclusionIn hypertensive environments, collateral vessels are less likely to develop, and S1PR1 may be involved in this phenomenon.

Efficacy of an Anti-Semaphorin 3A Neutralizing Antibody in a Male Experimental Retinal Vein Occlusion Mouse Model.

PurposeSemaphorin 3A (Sema3A) is a promising therapeutic target for macular edema in age-related macular degeneration, diabetic retinopathy, and retinal vein occlusion (RVO). Anti-vascular endothelial growth factors (anti-VEGFs) are the current standard of care for many retinal diseases. This study investigated the Sema3A neutralizing antibody BI-X and/or anti-VEGF therapy (aflibercept) in an RVO mouse model. Treatment efficacy was examined and grouped by timing subsequent to the RVO mouse model induction: efficacy against the onset of intraretinal edema 1 day postinduction and protective effects at 7 days postinduction.MethodsWe examined the changes in expression of Sema3A in the retina of an RVO mouse model. In addition, changes in expression of tumor necrosis factor (TNF)-α and semaphorin-related proteins (neuropilin-1 and plexin A1) in the retina upon treatment were analyzed by Western blotting. The effects of BI-X and/or aflibercept were evaluated using measures of retinal edema, blood flow, and thinning of the inner nuclear layer.ResultsInduction of vein occlusion in the RVO mouse model significantly increased Sema3A expression in the retina, particularly in the inner nuclear layer. BI-X was effective as a monotherapy and in combination with anti-VEGF therapy, demonstrating a beneficial effect on intraretinal edema and retinal blood flow. Moreover, in the RVO mouse model, BI-X monotherapy normalized the changes in expression of TNF-α and semaphorin-related proteins.ConclusionsThese findings support targeting Sema3A to treat intraretinal edema and retinal ischemia.

Inhibition of inflammatory cells delays retinal degeneration in experimental retinal vein occlusion in mice.

The role of microglia in retinal inflammation is still ambiguous. Branch retinal vein occlusion initiates an inflammatory response whereby resident microglia cells are activated. They trigger infiltration of neutrophils that exacerbate blood–retina barrier damage, regulate postischemic inflammation and irreversible loss of neuroretina. Suppression of microglia‐mediated inflammation might bear potential for mitigating functional impairment after retinal vein occlusion (RVO). To test this hypothesis, we depleted microglia by PLX5622 (a selective tyrosine kinase inhibitor that targets the colony‐stimulating factor‐1 receptor) in fractalkine receptor reporter mice (Cx3cr1 gfp/+) subjected to various regimens of PLX5622 treatment and experimental RVO. Effectiveness of microglia suppression and retinal outcomes including retinal thickness as well as ganglion cell survival were compared to a control group of mice with experimental vein occlusion only. PLX5622 caused dramatic suppression of microglia. Despite vein occlusion, reappearance of green fluorescent protein positive cells was strongly impeded with continuous PLX5622 treatment and significantly delayed after its cessation. In depleted mice, retinal proinflammatory cytokine signaling was diminished and retinal ganglion cell survival improved by almost 50% compared to nondepleted animals 3 weeks after vein occlusion. Optical coherence tomography suggested delayed retinal degeneration in depleted mice. In summary, findings indicate that suppression of cells bearing the colony‐stimulating factor‐1 receptor, mainly microglia and monocytes, mitigates ischemic damage and salvages retinal ganglion cells. Blood–retina barrier breakdown seems central in the disease mechanism, and complex interactions between different cell types composing the blood–retina barrier as well as sustained hypoxia might explain why the protective effect was only partial.

Investigation of retinal morphology alterations using spectral domain optical coherence tomography in a mouse model of retinal branch and central retinal vein occlusion.

Retinal vein occlusion is a leading cause of visual impairment. Experimental models of this condition based on laser photocoagulation of retinal veins have been described and extensively exploited in mammals and larger rodents such as the rat. However, few reports exist on the use of this paradigm in the mouse. The objective of this study was to investigate a model of branch and central retinal vein occlusion in the mouse and characterize in vivo longitudinal retinal morphology alterations using spectral domain optical coherence tomography. Retinal veins were experimentally occluded using laser photocoagulation after intravenous application of Rose Bengal, a photo-activator dye enhancing thrombus formation. Depending on the number of veins occluded, variable amounts of capillary dropout were seen on fluorescein angiography. Vascular endothelial growth factor levels were markedly elevated early and peaked at day one. Retinal thickness measurements with spectral domain optical coherence tomography showed significant swelling (p<0.001) compared to baseline, followed by gradual thinning plateauing two weeks after the experimental intervention (p<0.001). Histological findings at day seven correlated with spectral domain optical coherence tomography imaging. The inner layers were predominantly affected by degeneration with the outer nuclear layer and the photoreceptor outer segments largely preserved. The application of this retinal vein occlusion model in the mouse carries several advantages over its use in other larger species, such as access to a vast range of genetically modified animals. Retinal changes after experimental retinal vein occlusion in this mouse model can be non-invasively quantified by spectral domain optical coherence tomography, and may be used to monitor effects of potential therapeutic interventions.

Experimental retinal vein occlusion, a model of non‐neovascular microvascular remodeling

AbstractThe main cause of visual loss after retinal vein occlusion and diabetes is microvascular remodelling, a spectrum of functional and morphological changes affecting vessels. Some are beneficial, such as collateral vessel development. The other manifestations of microvascular remodelling are usually detrimental such as chronic rupture of the blood‐retinal barrier, capillary closure or macroaneurysms. The processes underlying microvascular remodelling are poorly understood, in part because of the absence of a clinically meaningful animal model. We have been investigating the effet of retinal vein occlusion in rodents using laser photocoagulation, which eanbled us to reproduce many of the features of human microvascular remodelling. Based on our experience, we will discuss issues related to interspecies variability and clinical relevance.

Evaluation of Ultrasound-Assisted Thrombolysis Using Custom Liposomes in a Model of Retinal Vein Occlusion

To study the potential efficacy of ultrasound (US) assisted by custom liposome (CLP) destruction as an innovative thrombolytic tool for the treatment of retinal vein occlusion (RVO). Experimental RVO was induced in the right eyes of 40 rabbits using laser photothrombosis; the US experiment took place 48 hours later. Rabbits were randomly divided into four equal groups: US+CLP group, US+saline group, CLP+sham US group, and no treatment group. The latter three groups acted as controls. Fundus fluorescein angiography and Doppler US were used to evaluate retinal blood flow. CLP-assisted US thrombolysis resulted in restoration of flow in seven rabbits (70%). None of the control groups showed significant restoration of retinal venous blood flow. US-assisted thrombolysis using liposomes resulted in a statistically significant reperfusion of retinal vessels in the rabbit experimental model of RVO. This approach might be promising in the treatment of RVO in humans. Further studies are needed to evaluate this approach in patients with RVO. Ultrasound assisted thrombolysis can be an innovative tool in management of retinal vein occlusion.

Effects of arteriolar constriction on retinal gene expression and müller cells in an experimental retinal vein occlusion

AbstractPurpose To investigate the effect of the laser‐induced arteriolar constriction (AC) on branch retinal vein occlusion (BRVO) induced Müller cell responses and alterations in gene expression of factors implicated in the development of edema.Methods In Brown‐Norway rats the BRVO was induced by laser photocoagulation of the veins in one half of the retina. AC of the afferent arterioles was performed 30 minutes later. The expression of Vegfa, Vegfb, Pedf, Kir4.1, Aqp4, Aqp1, Il1ß, and Il6 was determined with RT‐PCR in the retina and retinal pigment epithelium (RPE) after 1, 3 and 7 days. Potassium currents were recorded in Müller cells 3 days after BRVO. Immunostaining against GFAP, Aqp4 and Kir4.1 was performed on day 1 and 3.Results BRVO resulted in the neuroretinal transient upregulation of Vegfa on day 1. The expression of the Kir4.1, Aqp4, and Aqp1 channels were downregulated, and Il1ß and Il6 strongly upregulated, on day 1 and 3. The retinal distribution of GFAP and Aqp4 proteins remained unaltered, while the Kir4.1 protein displayed redistribution from a polarized to a uniform retinal distribution. Müller cells showed cellular hypertrophy and a decrease in potassium currents. AC accelerated the restoration of downregulated Kir4.1, Aqp4, and Aqp1 in the RPE, of Kir4.1 in the neuroretina and of upregulated Il6 in the neuroretina. AC did not influence the gliotic alterations of Müller cells and the redistribution of Kir4.1 protein.Conclusion The constriction of the afferent artery in the BRVO region had only marginal effect on the BRVO‐evoked alterations in retinal gene expression.

The Effect of Anti‐VEGF Treatment and Triamcinolone in Experimental Retinal Vein Occlusion

AbstractPurpose We investigated the effect of intravitreal injection of anti‐VEGF antibodies and triamcinolone acetonide (TA) in a rat model of central retinal vein occlusion (CRVO).Methods In one eye of adult Brown Norway rats (n=81) CRVO was induced with laser photocoagulation. Animals were divided into 3 groups (each n=27): 1. CRVO only without any treatment; 2. CRVO with anti‐VEGF antibodies; and 3. CRVO with TA. The injection of anti‐VEGF antibodies or TA was performed 15 minutes after CRVO induction. The gene expression was investigated using RT‐PCR in the neural retina 1, 3 and 7 days after CRVO. We analyzed the expression of VEGF‐A, VEGF‐B, PEDF; of channels implicated in retinal osmohomeostasis (Kir4.1, AQP4, AQP1), and of inflammatory factors IL‐1ß and IL‐6.Results CRVO induced a rapid transient upregulation of Vegfa, and a delayed upregulation of Pedf. Further strong, downregulation of Kir4.1, Aqp4, and Aqp1, and striking rapid upregulation of Il1ß and Il6 was observed. Anti‐VEGF antibodies fully prevented the upregulation of Vegfa and of Pedf, and decreased the upregulation of Il1ß. This treatment had no effect on the expression of Kir4.1, Aqp4, Aqp1, and Il6. Intravitreal TA reversed the downregulation of Kir4.1 and accelerated the normalization of the upregulated expression of Il1ß and Il6, but had no significant effect on the expression of Vegfa.Conclusion The anti‐VEGF treatment inhibits strongly the upregulation of Vegfa but influences only marginally the water channels or inflammatory factors. TA inhibits the expression of IL‐1ß and IL‐6, and has neuroprotective effects via improvement of retinal potassium homeostasis.

Effects of Huoxue Tongmai Lishui method on fundus fluorescein angiography of non-ischemic retinal vein occlusion: a randomized controlled trial

Huoxue Tongmai Lishui method, a traditional Chinese medicine treatment for eliminating water, activating and promoting blood circulation, could inhibit fundus hemorrhage on experimental retinal vein occlusion (RVO) with high obvious effective rate, and improve symptoms in traditional Chinese medicine. The action mechanism may be related to reducing plasma viscosity and non-perfusion area, and the formation of collateral circulation. To explore the therapeutic effects of Huoxue Tongmai Lishui method (Sanxue Mingmu Tablet) on fundus fluorescent angiograph of non-ischemic retinal vein occlusion (RVO). Thirty-four patients with non-ischemic RVO in Department of Ophthalmology, the First Affiliated Hospital, Hunan University of Traditional Chinese Medicine from April 2005 to April 2009 were included. All the patients were diagnosed as qi stagnation and blood stasis syndrome or hyperactivity of liver yang syndrome, and they were randomly divided into two groups, with 17 eyes of 17 patients in treatment group treated by Sanxue Mingmu Tablet combined with conventional treatment, and 18 eyes of 17 patients in control group treated by Xueshuantong Tablet combined with conventional treatment. The patients were treated for two months. Fundus colour photography, and fundus fluorescent angiograph were detected in two groups before and after the treatment. The curative effect of Sanxue Mingmu Tablet was better than that of Xueshuantong Tablet. Huoxue Tongmai Lishui method could significantly shorten the retinal circulation time, reduce the non-perfusion area, decrease the formation of angiogenesis and promote the formation of collateral circulation. Huoxue Tongmai Lishui method is an effective traditional Chinese medicine treatment with high obvious effective rate in reducing non-perfusion area and avoiding venous occlusion and formation of collateral circulation.

Inflammatory factors in experimental retinal vein occlusion

Abstract Purpose Vascular endothelial growth factor (VEGF) is a key player in the development of macular edema (ME) in patients with retinal vein occlusion (RVO). In addition to VEGF, various other factors are altered in the hypoxic retina and influence the development of ME. In a rat model of RVO, we determined the changes in the gene expression of factors implicated in the development/resolution of ME (VEGF‐A, PEDF, IL‐6, Il‐1β, potassium und water channels) in the retina and pigment epithelium (RPE). Methods In one eye of Long‐Evans rats (n=30), retinal veins near the optic nerve head were photocoagulated using a blue‐green argon laser. Untreated eyes served as controls. The eyes were enucleated 1, 3 and 7 days after laser treatment, and the mRNA levels were determined with real‐time PCR. Results In the neural retina, VEFG expression showed fast upregulation at 1 day after RVO, and returned to the control level after 3 days. The expression of VEGF was not altered in the RPE. Potassium and water channels were downregulated in both tissues through the entire time period investigated. IL‐6 and IL‐1β were rapidly and strongly upregulated in the retina and RPE (to levels 80‐times higher as control) within 1 day after RVO, and decreased only slowly after 7 days. Conclusion In RVO, there is fast and transient upregulation of the expression of VEGF, which is dominant for the acute stage of the disease. The strong and long‐lasting upregulation of IL‐6 and IL‐1β suggests that inflammatory factors play an important role in chronic hypoxia.

Natural course of experimental retinal vein occlusion in rabbit; arterial occlusion following venous photothrombosis

Retinal vein occlusion (RVO) is the second leading cause of vascular eye disease. Currently there is no definite treatment for this condition. Animal models could be potentially helpful in developing new treatments; however, it is essential to understand the differences these models may have with human RVO. The aim of our study was to examine the course of experimentally created retinal vein occlusion (RVO) in rabbits. Twenty-nine pigmented rabbits were included in the study. RVO was created in all using an argon green laser following intravenous injection of Rose Bengal. A laser was applied to all major veins at the optic disc margin to mimic central retinal vein occlusion. Animals were followed-up for a maximum of 2 months. Immediately following laser application, blood flow ceased or the flow was extremely slow in the retinal veins in all cases. At day 2 post laser, 86% showed significant retinal hemorrhages. On FA, no retinal blood flow was observed in the eye (neither arteries nor veins) in the majority of rabbits. Between weeks 1 and 3, laser sites reopened and partial or complete revascularization of both retinal arteries and veins occurred; however, the vascular pattern was abnormal. RVO in rabbits has a different course than in human and it can be classified into three stages. At stage 1 (the first few days after laser photothrombosis), there is a retrograde propagation of the blood clot in the retinal veins that extends to the retinal arteries and choriocapillaries. As a result, there is no retinal blood flow at this stage in most cases. At stage 2 (between weeks 1 and 3), partial or complete revascularization occurs but the vessels have an abnormal pattern. At stage 3 (after week 3) no significant change takes place.

This issue of Acta

This issue of Acta is dominated by paediatric ophthalmology. The cover illustrations show fundus photographs and optical coherence tomography (OCT) images from a girl with 3-hydroxyacyl-CoA dehydrogenase deficiency as reported by Teär Fahnehjelm et al. in this issue. Teär Fahnehjelm discusses the role of paediatric ophthalmologists and their interaction with paediatricians. The second editorial is the yearly report by the Editor in Chief on the state of the journal. Berker & Batman, in Ankara, review several approaches to the surgical treatment of central retinal vein occlusion. Teär Fahnehjelm et al., in Stockholm, found dry eye to be common in children treated with stem-cell transplantation, particularly in patients treated with high levels of cyclosporine A. These children need intensive ophthalmological care. Lindqvist et al., in Trondheim, found that children born prematurely with very low birth weight are at risk for poor binocular function and eye movement in adolescence, whereas this does not apply to very low birth weight children who are born at term. Lavezzo et al., in São Paulo, found that newborn babies blink their eyes slower and less frequently than 4–6-year-old children. Uretmen et al., in Turkey, report that accommodative esotropia developed in 50% of children who underwent surgical treatment for presumed infantile esotropia. Teär Fahnehjelm et al., in Sweden, describe the ocular characteristics of a group of children with 3-hydroxyacyl-CoA dehydrogenase deficiency with variable degrees of chorioretinal pathology and visual impairment. Soliman et al., in Copenhagen and Egypt, propose that OCT analysis can predict the visual outcome 1 month following laser photocoagulation for diffused diabetic macular oedema. Maca et al., in Vienna, used the retinal thickness analyser to demonstrate that cystoid macular oedema is common in children with uveitis – even some with good visual acuity. Mahdizadeh et al., in Iran, found that retinal cryopexy did not benefit the anatomical reattachment rate from scleral buckling surgery. Donati et al., in Geneva, found that both necrosis and apoptosis are involved in neuronal cell death following experimental retinal vein occlusion in pigs. Krøyer et al., in Copenhagen, described the effect of acute retinal pigment epithelial loss, which destroyed scotopic but not photopic retinal function in a 68-year-old woman. Bertschinger et al., in Geneva, used the Vryghem macular function test and found this to be reliable in predicting postoperative visual acuity after cataract surgery. Cillino et al., in Italy, found Gore-Tex® implants to be useful adjuvants in glaucoma filtration surgery. Yoeruek et al., in Tübingen, used Avastin® eyedrops to reduce corneal damage and neovascularization following experimental chemical burns to the cornea. Al-Jamal & Kivelä describe an optic nerve tumour leading to progressive visual loss in a young man. I hope that this issue of Acta offers an opportunity to brush up on our knowledge in paediatric ophthalmology and provides educational opportunities in all subspecialties of ophthalmology.

Retinal vein cannulation with prolonged infusion of tissue plasminogen activator (t-PA) for the treatment of experimental retinal vein occlusion in dogs

To evaluate the feasibility, safety, and efficacy of local thrombolytic agents directly injected into occluded retinal veins in an experimental animal model. Experimental animal study. This experimental study was performed in two phases. In phase 1, 15 enucleated porcine eyes and 8 in vivo canine eyes were used for the development of the instrumentation and surgical technique required for retinal vein cannulation with prolonged intravascular infusion. In phase 2 of this study, experimental branch retinal vein occlusion was photo-chemically created using an intravenous injection of rose bengal followed by diode laser photocoagulation in eight eyes of eight dogs. Four eyes were treated by retinal vein cannulation and an injection of tissue plasminogen activator (t-PA) using a specifically designed microcatheter, while the remaining four eyes were untreated (control group). The total amount of t-PA injected intravenously ranged from 400 to 1000 mug, infused over a period ranging from 25 to 45 minutes with a mean pressure of 40 psi, resulting in a mean injection flow rate of 0.05 ml/min. The dogs underwent clinical examination, fluorescein angiography, and histologic examination. Main outcome measures were: Achievement of prolonged intravascular infusion of t-PA, changes in fundus appearance, fluorescein angiography, and histology. A microcatheter instrument and a surgical technique for retinal vein cannulation with prolonged intravascular infusion were developed. Cannulation and t-PA infusion for a period of at least 30 minutes was achieved in all four treated eyes with experimental branch retinal vein occlusion. No complications were recorded in all treated eyes. One week and 1 month postoperatively, treated eyes exhibited marked decreases in retinal hemorrhages, retinal vein dilation, and tortuosity, whereas nontreated eyes exhibited persistence of these findings. Fluorescein angiography demonstrated improved circulatory flow in treated relative to nontreated eyes. Histologic analysis confirmed the presence of thrombi in nontreated eyes only. Retinal vein cannulation with prolonged intravascular injection of t-PA is feasible and safe, and this may offer a new treatment option for retinal vein occlusion.

Quantitative evaluation for blood-retinal barrier breakdown in experimental retinal vein occlusion produced by photodynamic thrombosis using a new photosensitizer

Purpose. To establish a rat model of retinal vein occlusion (RVO), we applied photodynamic thrombosis using a new photosensitizer. By measuring the breakdown of the blood-retinal barrier (BRB), we evaluated the model quantitatively. We also investigated how hypertension and retinal pigment epithelium (RPE) influence the breakdown of BRB after RVO. Methods. We modified a slit lamp biomicroscope for photodynamic thrombosis. The light source was changed from white light to argon laser, which made it possible to perform fluorescein angiography (FAG) simultaneously during photodynamic thrombosis. We irradiated with a continuous diode laser to occlude three retinal veins in a rat after PAD-S31 injection. The breakdown of BRB was quantitated by measuring extravasated Evans blue dye in albino and pigmented rats. We compared hypertensive rats (SHR) to nor-motensive rats (WKY) and sodium iodate-treated rats to normal rats. Results. High photosensitivity of PAD-S31 made it possible to occlude any retinal veins within 120 seconds at a low dose of 10 mg/kg without retinal thermal burn at the occlusion site. Simultaneous FAG enabled us to observe the formation of thrombus during diode laser irradiation. Our measured value of intraretinal Evans blue correlated with the range of serous retinal detachment. Both albino and pigmented rats demonstrated stable and constant values of Evans blue. SHR recovered from the breakdown of BRB after venous occlusion more slowly than WKY. Sodium iodate-treated rats had smaller breakdowns of BRB and recovered earlier than normal rats. Conclusions. In this study, we established the stable and constant rat model of RVO efficiently by using a new photosensitizer. Our simultaneous FAG method was considered to have an advantage of several potential clinical applications. Our rat model of RVO allows us to study factors associated with the recovery from damage by RVO.

Alterations in protein tyrosine kinase pathways following retinal vein occlusion in the rat

Purpose. To determine whether an experimental retinal vein occlusion in the rat activates protein tyrosine kinase pathways and increases angiogenic growth factors in the retina. Methods. Retinal vein occlusion (RVO) was induced in the rat retina with argon laser photocoagulation. Retinas were collected at 2 days, 1, 2, and 4 weeks after RVO and divided into halves: one half represented an area within the distribution of the occluded vein [RVO(IN)] and the other half represented an area outside the distribution of the occluded vein [RVO(OUT)]. RVO(IN) and (OUT) were examined by western blot analysis of tyrosine-phosphorylated proteins, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and 3 signal proteins in the tyrosine kinase pathways: phospholipase C? (PLC?), phosphatidylinositol 3-kinase (PI3K), and mitogen-activated protein kinase (MAPK). Results. RVO caused a severe capillary nonperfusion in RVO(IN). Overall tyrosine-phosphorylated proteins were increased after RVO, especially in RVO(IN) at 2 days and 1 week. VEGF and bFGF were markedly increased in RVO(IN) at 2 days and 1 week. Tyrosine-phosphorylated PLC?, PI3K, and MAPK were also increased in RVO(IN) at these time points. Conclusions. RVO caused an increase in overall protein tyrosine phosphorylation in the rat retina. This increase was associated with an increase in angiogenic growth factors (VEGF and bFGF). These results suggest that protein tyrosine kinase pathways are activated during retinal ischemia and may play a role in mitogenesis of vascular endothelial cells and other responses in the retina after RVO.

Ultrasound enhanced thrombolysis in experimental retinal vein occlusion in the rabbit

AIMSTo investigate if it was possible to lower the dose of streptokinase and maintain an effective thrombolysis by adding pulsed low energy ultrasound.Methods—53 retinal veins in 27 rabbits were occluded...

Preretinal neovascularization induced by experimental retinal vein occlusion in albino rats.

Retinal ischemia and neovascularization have been demonstrated in several animal models. To determine 1) whether the retinal or preretinal neovascularization can be induced in albino rats by retinal vein occlusion and 2) the type and rate of occurrence on neovascularization, we occluded retinal veins in albino rats by photodynamic thrombosis. After anesthesia, each of 36 rats received an injection of rose bengal photosensitive dye, and their veins underwent argon green laser treatment. Half or all the major retinal veins were occluded in 12 eyes and in 24 eyes, respectively. Ten control rats underwent the same procedures but the laser beam was directed between major retinal vessels. In 46 control eyes, rose bengal dye was seen to have perfused without laser treatment. Retinal detachment developed in most vein occluded eyes within one day of venous occlusion, which was confirmed by fluorescein angiography. On follow-up at two weeks, only four of 24 eyes (16.7%) had undergone occlusion of all retinal veins showed new preretinal vessels on the optic disc. In these four eyes, severe disturbance of both retinal arterial and venous blood flow was observed, but no other eyes showed such severe combined disturbance. These data suggest that preretinal neovascularization in albino rats can be induced by this minimally traumatic method and that venous occlusion is severe enough to compromise arterial blood flow for a certain threshold period, thus inducing the development of preretinal neovascularization.

Ocular neovascularization. Tissue culture studies.

The proliferative activity of a number of intraocular fluids, bovine retinal extract, and normal serum (from humans and cynomolgus monkeys) was investigated by in vitro tissue culture studies, with the use of tritiated thymidine incorporation by the cultured endothelial cells of human umbilical veins. There was increased tritiated thymidine incorporation by (1) the aqueous, vitreous, and intraocular fluid (IOF) (which filled the eye after lensectomy and vitrectomy) removed from cynomolgus monkey eyes with iris neovascularization or with neovascular glaucoma (NVG) that developed after experimental retinal vein occlusion, (2) by aqueous and vitreous removed from human eyes with NVG or proliferative diabetic retinopathy; (3) by the serum, and (4) by the bovine retinal extract. However, tritiated thymidine incorporation was not increased by the normal aqueous, vitreous, or IOF.

Experimental retinal branch vein occlusion in rhesus monkeys. III. Histopathological and electron microscopical studies.

Experimental retinal vein occlusion in monkeys was followed by an immediate increase in capillary permeability which was accompanied by retinal oedema. This functional capillary change was followed at about 6 hours after occlusion by structural damage to the capillary wall. Thrombus formation occurred in the damaged vessels, and areas of stasis were thus produced with associated retinal haemorrhages. Finally, there was complete loss of the capillary endothelium and pericytes, and the acellular capillaries were invaded by proliferating glial cell processes, so producing permanent capillary closure.

Experimental Retinal Vein Occlusion and Treatment with Fibrinolysin

Experimental Retinal Vein Occlusion and Treatment with Fibrinolysin